Abstract
To explore more potent N-acylimidazole analogues of CDDO than CDDO-Im, which is one of the most potent compounds in several widely used bioassays related to protection against inflammation and carcinogenesis; we have synthesized and evaluated five new N-acyl(acetylenic)imidazole analogues. Among them, 4-ethynylimidazole 4 is nearly equivalent to CDDO-Im in potency in these bioassays. Remarkably, the solid form of 4 is more stable than that of CDDO-Im. These findings suggest that 4 is a very promising anti-inflammatory and cytoprotective agent and its further preclinical evaluation is warranted.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents / chemical synthesis*
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Anti-Inflammatory Agents / chemistry
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Anti-Inflammatory Agents / pharmacology
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Cell Line, Tumor
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Cytoprotection / drug effects
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Heme Oxygenase-1 / metabolism
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Imidazoles / chemical synthesis*
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Imidazoles / chemistry*
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Imidazoles / pharmacology
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Interferon-gamma / metabolism
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Mice
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NAD(P)H Dehydrogenase (Quinone) / metabolism
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Nitric Oxide / metabolism
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Oleanolic Acid / analogs & derivatives*
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Oleanolic Acid / chemical synthesis
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Oleanolic Acid / chemistry
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Oleanolic Acid / pharmacology
Substances
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1-(2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl)-4-ethynylimidazole
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1-(2-cyano-3,12-dioxooleana-1,9-dien-28-oyl) imidazole
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Anti-Inflammatory Agents
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Imidazoles
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Nitric Oxide
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Oleanolic Acid
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Interferon-gamma
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Heme Oxygenase-1
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NAD(P)H Dehydrogenase (Quinone)
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Nqo1 protein, mouse